Primary cardiac allograft failure after donor carbon monoxide poisoning treated with biventricular assist device.

Because of the current donor shortage, organ selection criteria are being progressively liberalized. We present a case of carbon monoxide poisoning in a multiorgan donor that led to primary cardiac allograft failure. A biventricular assist device was used as a bridge to recovery.

Should we use video-assisted endoscopic vein harvesting as a standard technique?

BACKGROUND: To investigate the feasability and results of endoscopic vein harvesting (EVH) using the Vasoview Uniport system (Guidant Corporation, Menlo Park,CA). Can this technique be used as a standard technique for vein harvesting in coronary artery bypass surgery (CABG) or is it too time consuming? Do smaller incisions result in less morbidity and discomfort? METHODS: From October 1998 to May 1999, 158 patients who underwent CABG with venous grafts, in addition to arterial grafts, formed the study population for EVH. In group A (n=131) the vein was harvested with the Vasoview Uniport System. In group B (n=27) the vein was harvested by a conventional open technique with interrupted incisions because of unavailability of the equipment. Recordings were made on vein length, harvest time, length of incision, and complications. RESULTS: In none of the patients in group A was a conversion to the open technique necessary. In 72/131, pure EVH was used. In 59/131 an additional incision below the knee was used for harvesting extra vein length. Mean harvested vein graft length (cm) was 35.9 (range 18-56) in group A and 30.6 (range 16-51) in group B, and mm of vein harvested/min was 77 and 71 in group A and B. Mean time for harvesting and closing (min) was 56.1 (range 14-120) SD 20.4 and 78.3 (range 37-129) SD 26 for a mean length of incision (cm) of six (range 2-19) and 27 (range 12-54). Wound complications at postoperative day three at discharge, and after six weeks were seen in 30 (23%), 27 (20%) and four (4%) patients of group A, and in five (18%), five (18%) and four (23%) of group B. CONCLUSIONS: Despite a learning curve in using endoscopic techniques, the total procedural time for EHV is acceptable and even shorter than open harvesting. Most of the time is gained in closure of the wound. Hematoma formation is the most common peroperative complication, but diminishes with experience. The absence of postoperative edema after EVH is striking. Despite the higher costs for disposable material, we have adopted EVH as a standard technique since patient and surgeon satisfaction have improved substantially.

Screening for solid organ malignancies prior to heart transplantation.

BACKGROUND: Prognosis of solid organ cancer in immunosuppressed hosts is generally dismal. Therefore, every effort to identify patients with asymptomatic carcinomas before transplantation should be encouraged. METHODS: Sixty-seven patients referred for heart transplantation were examined adhering to the scheme proposed at the 24th Bethesda Conference. To increase the sensitivity of this work-up, the following items were added: tumor marker assays (prostate-specific antigen in males, carcino embryogenic antigen), abdominal ultrasound, CT scan of the abdomen and the thorax, mammography/echography of the breasts, PAP smear, colonoscopy if carcino embryogenic antigen abnormal or occult blood in stool, prostate echography if prostate-specific antigen abnormal or prostate hypertrophy. RESULTS: Carcinoma was detected in 10 of the 67 patients; for 8 patients of this cancer group, transplantation was denied. Importantly, 9 of the 10 malignancies were detected by means of the diagnostic items that were added to the standard screening protocol. There were no significant differences between the cancer and the non-cancer group regarding mean age, sex, etiology of heart failure, and smoking history. Stratifying patients in younger (i.e., < or =54 years) and older (i.e., > or =55 years) age groups showed a significantly greater proportion of older patients in the cancer group (8/10=80%) compared to the non-cancer group (25/57=44%), P=0.04. After a mean follow-up of 34 months, 5 of the 36 transplanted patients developed a malignancy (4 skin carcinomas, 1 non-Hodgkin lymphoma). There have been no malignancy-related deaths until now. CONCLUSION: The importance of a thorough screening program in the triage of candidates with preexisting malignancies, especially in an older patient population, is illustrated in this report.

Establishment of serum-free pre-colony forming unit assays for differentiation of primitive hematopoietic progenitors: serum induces early macrophage differentiation and inhibits early erythroid differentiation of CD34++CD38- cells.

In this report we show that serum has differentiation-inducing effects on primitive hematopoietic progenitor cells with the CD34++CD38- immunophenotype. Using the pre-colony forming unit (pre-CFU) assay as a model for early myelopoiesis, we compared the effects of serum-containing and serum-free media and evaluated different cytokine cocktails [interleukin (IL)-1, IL-3, IL-6, kit ligand with and without the Flt3/Flk2 ligand (FL)]. In this assay, pre-CFUs are defined as cells unable to form colonies when plated directly in semi-solid assays, but which can differentiate into CFUs when cultured in liquid medium containing early-acting cytokines. In one of the investigated serum-free media, the average myeloid expansion in liquid medium reached up to more than 50% of that obtained in serum-containing medium. In addition, our experiments revealed differences in the clonogenic output between cells cultured in serum-free medium and those cultured in serum-containing medium, demonstrating that serum has a monocyte differentiation-inducing effect on primitive hematopoietic progenitors. Also in serum-free medium, higher proportions of erythroid progenitors were generated. These differentiation-inducing effects of serum further emphasize the need for serum-free culture protocols for hematopoietic graft engineering. Addition of FL to the culture media ameliorated cellular expansion and resulted in a decrease in the proportion of erythroid and granulocyte progenitors and an increase in the proportion of monocyte progenitors. In conclusion, this study shows that good serum-free conditions are available for differentiation assays with primitive hematopoietic progenitors and demonstrates that serum and FL have biasing effects on the initial phase of hematopoietic differentiation, favoring the monocyte lineage.

Emergency ventricular assist device: better survival rates in non-post cardiotomy-related cardiogenic shock.

OBJECTIVE: The Abiomed BVS 5000 ventricular assist device (VAD) has been approved in Belgium for emergency cardiac support in patients with postcardiotomy failure with the aim of native heart function recovery. Other indications have emerged from world wide experience, but the indication and usefulness of emergency implantation of assist devices is often debated. METHODS: To decide which patients benefit most from emergency ventricular assist device implantation, we retrospectively reviewed our results of mechanical circulatory support with Abiomed in 20 patients over a 4-year period. Fifteen patients with mean age 58 +/- 6 years experienced postcardiotomy failure and underwent biventricular assist device (BVAD) implantation (group A), after elective (n = 9) or after emergency coronary artery bypass grafting (CABG) (n = 6). Five patients (group B), with mean age 35 +/- 19 years, had an implantation for other underlying conditions: hypertrophic cardiomyopathy (n = 3), myocarditis (n = 1) and primary cardiac allograft failure (n = 1). RESULTS: Of these two groups, eight and two patients respectively needed cardiopulmonary resuscitation before VAD implantation. The mean duration of support in both groups was 5.8 (range 12 h-13 days) and 4.4 days (range 2 h-9 days) respectively. Six and two patients could be weaned from the device and nine and one patients respectively, died on the device. Two patients in group B underwent successful heart transplantation and four patients in group A died after weaning. Two patients in the postcardiotomy group and four patients in group B survived (13% and 80%) with an overall survival and discharge rate of 30%. CONCLUSION: Although sample sizes are small, better survival rates with emergency Abiomed BVS 5000 implantation were obtained in the non postcardiotomy group (group B). For patients in the postcardiotomy group, outcome was negatively influenced by cardiac arrest and resuscitation before urgent CABG. Since death is the only alternative for these patients in cardiogenic shock and organ recovery cannot be predicted, we continue to consider emergency VAD implantation in this patient population.

Cardiac surgery in octogenarians.

OBJECTIVE: The elderly segment of the Western population is increasing rapidly, and cardiac surgeons are being asked to consider the very elderly for cardiac surgery. Our objective was to obtain data on the outcome of cardiac surgery in octogenarians in order to improve the indication for surgery and to give more accurate information to patients, family and general practitioners. METHODS AND RESULTS: From January 1990 through December 1998, 127 octo- and nonagenarians (age 80-94, mean 82.2 years) underwent cardiac surgery (coronary artery bypass grafting, valve surgery and aortic surgery) at the University Hospital of Antwerp. A retrospective review of the patients' medical records was performed. Follow-up information was obtained by mail or telephone from each patient's primary physician or cardiologist. Hospital mortality was 7.1% (9/127) and late mortality (mean follow-up 2 years) was 23% (30/127). Actuarial survival at 108 months was 70% (90/127). Eighty-three percent of the patients were having class III or IV anginal symptoms before operation. At follow-up 76% of the survivors were in NYHA class I or II. CONCLUSION: Cardiac surgery in the very old often permits survival with improved symptoms. Therefore surgery should not be refused solely because of old age.

Chronic osteomyelitis after sternotomy.

Two patients with chronic sternal osteomyelitis after an initially uncomplicated coronary artery bypass grafting (CABG) operation are described. Chronic osteomyelitis, caused in both cases by Pseudomonas aeruginosa, occurred six and four months after CABG respectively. Because chronic infection failed to respond to local wound care and medical therapy, more radical treatment was needed. Steel wires were removed and surgical debridement was performed. In one patient, an additional omental transposition was performed. In both cases radical debridement in combination with antibiotics successfully eradicated the infection.

Generation of T cells from adult human hematopoietic stem cells and progenitors in a fetal thymic organ culture system: stimulation by tumor necrosis factor-alpha.

To investigate the T-lymphopoietic capacity of human adult bone marrow (ABM) hematopoietic progenitor cells, CD34+Lin-, CD34+CD38+, and CD34++CD38- cells were cultured in a severe combined immunodeficient (SCID) mouse fetal thymic organ culture (FTOC). Direct seeding of these progenitors resulted in a moderate to severe cell loss, particularly for the CD34++CD38- cell fraction, and T cells could only be generated from the CD34+Lin- fraction. Preincubation for 36 hours with interleukin-3 (IL-3) and stem cell factor (SCF) led to an improved cell survival and proliferation, although T-cell development was seen only in the CD34+Lin- fraction. Addition of tumor necrosis factor (TNF)-alpha to IL-3 + SCF-supplemented preincubation medium resulted in optimal cell survival, cell proliferation. and T-cell generation of all 3 cell fractions. The TNF-alpha effect resulted in an up-regulation of CD127 (ie, the IL-7 receptor alpha-chain) in a small subset of the CD34+ cells. No evidence could be generated to support the possibility that TNF-alpha inhibits a cell population that suppresses T-cell differentiation. A quantitatively different T-cell generation potency was still seen between the 3 subpopulations: CD34+Lin- (100% success rate) > CD34+CD38+ (66%) > CD34++CD38- (25%). These data contrast with our previous findings using fetal liver and cord blood progenitors, which readily differentiate into T-lymphocytes in FTOC, even without prestimulation with cytokines. Our results demonstrate that adult CD34++CD38- cells, known to contain hematopoietic stem cells, can differentiate into T-lymphocytes and that a significant difference exists in T-lymphopoietic activity of stem cells derived from ontogenetically different sources. (Blood. 2000;95:2806-2812)

Coronary artery bypass grafting on the beating heart using the Octopus method.

STUDY OBJECTIVE: To study the usefulness and effectiveness of off-pump coronary bypass grafting with the Octopus heart stabilizing device. METHOD: The files of thirty-one patients undergoing coronary artery bypass with the aid of the Octopus heart stabilizing device between April 1996 and October 1998 were studied retrospectively. Patients were divided into group A (n = 23), patients with single or double vessel disease and technically suitable coronary lesions for off-pump procedure and group B (n = 8), patients with multiple vessel disease considered to be with excessive risk for cardiopulmonary bypass due to poor general condition combined with renal failure and/or chronic obstructive pulmonary disease. Standard median sternotomy (n = 27), lateral thoracotomy (n = 1) or minithoracotomy (n = 3) were performed for access and for harvesting the left internal mammary artery (LIMA). MEASUREMENTS AND RESULTS: The mean number of bypasses was 1.2 and 1.1 in groups A and B, respectively. Thirty patients received a LIMA graft to the left anterior descending artery (LAD). Homologous blood transfusions were needed in five patients (21%) in group A and four (50%) in group B. There were no wound infections or neurologic complications. All patients in group A survived and are asymptomatic. One patient in group B died of septic shock, two have residual angina pectoris or dyspnea, and five are asymptomatic. CONCLUSION: Coronary artery bypass using the Octopus heart stabilizing device proved to be a safe and effective technique resulting in complete revascularization in group A patients with no mortality. Incomplete revascularization may offer a substantial benefit to patients who cannot tolerate cardiopulmonary bypass due to poor general condition. We prefer median sternotomy, allowing precise harvesting of the internal mammary artery and more precise anastomoses without increased morbidity.

Spontaneous dissection of three major coronary arteries subsequent to cystic medial necrosis.

This case report describes the devastating consequences of spontaneous coronary dissection in a 36-year-old female patient. Surgical revascularization was attempted, but diffuse myocardial infarction developed. The patient was bridged to heart transplantation but died secondary to multiple organ failure. To our knowledge, this is the only reported case of spontaneous dissection of the three main coronary arteries due to severe cystic medial necrosis.

The effects of beta-adrenergic stimulation on the length-dependent regulation of myocardial function in coronary surgery patients.

UNLABELLED: Increasing cardiac load by leg elevation identifies patients with load-dependent impairment of left ventricular (LV) function. This impairment is related to a deficient length-dependent regulation of LV function. We investigated the effects of dobutamine on length-dependent regulation of LV function in coronary surgery patients (n = 25). High-fidelity LV pressure tracings were obtained at end-expiration, while hearts were paced at a fixed rate of 90 bpm. Effects of leg elevation on contraction and relaxation were compared before and during dobutamine 5 microg x kg(-1) x min(-1). Effects on contraction were evaluated by analysis of changes in dP/dtmax. Effects on relaxation were assessed by analysis of R (slope of the relation between the time constant of isovolumic relaxation and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r. The effects of leg elevation on variables of contraction and relaxation were coupled. We found a close relationship between changes in dP/dtmax and individual values of R (r = 0.84; P < 0.001). Dobutamine improved myocardial function and accelerated LV pressure decrease. Under dobutamine, the increase in dP/dtmax with leg elevation was larger (P < 0.001) and load dependence of LV relaxation was reduced (P = 0.001). Dobutamine improved the effects of leg elevation on LV function, reflecting improved length-dependent regulation of LV function. IMPLICATIONS: This study demonstrated that beta-adrenoreceptor stimulation with dobutamine improved length-dependent regulation of myocardial function assessed during leg elevation in cardiac surgical patients.

Length-dependent regulation of left ventricular function in coronary surgery patients.

BACKGROUND: Load-dependent impairment of left ventricular (LV) function was observed after leg elevation in a subgroup of coronary surgery patients. The present study investigated underlying mechanisms by comparing hemodynamic effects of an increase in LV systolic pressures with leg elevation to effects of a similar increase in systolic pressures with phenylephrine. METHODS: The study was performed in patients undergoing elective coronary surgery prior to cardiopulmonary bypass. High-fidelity LV pressure tracings (n = 25) and conductance LV volume data (n = 10) were obtained consecutively during leg elevation and after phenylephrine administration (5 microg/kg). RESULTS: Leg elevation resulted in a homogeneous increase in end-diastolic volume. The change in stroke volume (SV), stroke work (SW) and dP/dtmax was variable, with an increase in some patients but no change or a decrease in other patients. For a matched increase in systolic pressures, phenylephrine increased SW and dP/dtmax in all patients with no change in SV. Load dependence of relaxation (slope R of the tau-end-systolic pressure relation) was inversely related for changes in SV, SW, and dP/dtmax with leg elevation but not with phenylephrine. CONCLUSIONS: The different effects of leg elevation and phenylephrine suggest that the observed decrease in SV, SW, and dP/dtmax with leg elevation in some patients could not be attributed to an impaired contractile response to increased systolic LV pressures. Instead, load-dependent impairment of LV function after leg elevation appeared related to a deficient length-dependent regulation of myocardial function.

Contraction-relaxation coupling and impaired left ventricular performance in coronary surgery patients.

BACKGROUND: Dependence of left ventricular (LV) relaxation on cardiac systolic load is a function of myocardial contractility. The authors hypothesized that, if a tight coupling would exist between LV contraction and relaxation, the changes in relaxation rate with an increase in cardiac systolic load would be related to the changes in LV contraction. METHODS: Coronary surgery patients (n = 120) with preoperative ejection fraction >40% were included. High-fidelity LV pressure tracings (n = 120) and transgastric transesophageal echocardiographic data (n = 40) were obtained. Hearts were paced at a fixed rate of 90 beats/min. Effects on contraction were evaluated by analysis of changes in dP/dt(max) and stroke area. Effects on relaxation were assessed by analysis of R (slope of the relation between tau and end-systolic pressure). Correlations were calculated with linear regression analysis using Pearson's coefficient r. RESULTS: Baseline LV end-diastolic pressure was 10+/-3 mm Hg (mean +/- SD). During leg raising, systolic LV pressure increased from 93+/-9 to 107+/-11 mm Hg. The change in dP/dt(max) was variable and ranged from -181 to +254 mm Hg/s. A similar variability was observed with the changes in stroke area, which ranged from -2.0 to +5.5 cm2. Changes in dP/dt(max) and in stroke area were closely related to individual R values (r = 0.87, P<0.001; and r = 0.81, P<0.001, respectively) and to corresponding changes in LV end-diastolic pressure (r = 0.81, P< 0.001; and r = 0.74, P<0.001, respectively). CONCLUSIONS: A tight coupling was observed between contraction and relaxation. Leg raising identified patients who developed a load-dependent impairment of LV performance and increased load dependence of LV relaxation.

Nonviral transfection of distinct types of human dendritic cells: high-efficiency gene transfer by electroporation into hematopoietic progenitor- but not monocyte-derived dendritic cells.

Human dendritic cells (DC) are highly professional antigen presenting cells for the priming of naive cytotoxic T cells. Gene transfer in DC would be a useful strategy to load DC with relevant de novo synthesized antigens for immunotherapeutical purposes. As a first step towards a DC-based gene therapy, we examined the efficiency of nonviral transfection in different types of cultured human dendritic cells with a humanized red-shifted green fluorescent protein reporter gene. Plasmid DNA transfection by electroporation or lipofection was used to transfect CD34+ progenitor cell-derived DC (PC-DC) and Langerhans' cells (PC-LC), as well as monocyte-derived DC (Mo-DC). While lipofection was unsuccessful in all types of DC, we obtained high-efficiency gene transfer by electroporation in PC-LC (16%) and PC-DC (12%). In contrast, electroporation was strikingly less efficient in Mo-DC (< or = 2%). The potent allostimulatory capacity of DC was still retained in electroporated PC-DC and PC-LC. In conclusion, electroporation of antigen expressing plasmid DNA is an efficient tool for nonviral gene transfer in PC-DC and PC-LC, but not in Mo-DC and could be useful for the development of DC-based tumor immunotherapy.

CD34++ CD38- and CD34+ CD38+ human hematopoietic progenitors from fetal liver, cord blood, and adult bone marrow respond differently to hematopoietic cytokines depending on the ontogenic source.

CD34++ CD38- and CD34+ CD38+ hematopoietic progenitor cells (HPCs) from human fetal liver (FL), cord blood (CB), and adult bone marrow (ABM) were isolated and investigated for their growth characteristics, cytokine requirements and response to two modulators of early hematopoiesis, interferon (IFN)-gamma and macrophage inflammatory protein (MIP)-1alpha. We observed first that a significantly lower percentage of CD34++ cells were CD38- in ABM than in FL and CB. Second, the functional differences between CD34++ CD38- and CD34+ CD38+ cells were less pronounced in FL and CB than in their ABM counterparts. Third, an inverse correlation was found between growth factor response and the ontogenic age of HPCs, and a direct correlation was noted between cytokine requirements and the ontogenic age of HPCs. Fourth, spontaneous colony formation in a classic semisolid culture system was reproducibly obtained only in the ontogenically earliest cells, that is, in FL but not in CB and ABM, in which no such spontaneous colony formation was observed. Fifth, the modulatory effects of IFN-gamma and MIP-1alpha were qualitatively different depending on the ontogenic age of the progenitor source: whereas IFN-gamma was only a selective inhibitor of primitive CD34++ CD38- ABM progenitor cells, it inhibited both CD34++ CD38- and CD34+ CD38+ FL and CB cells to the same extent. In contrast to the effects of MIP-1alpha on ABM, we could not find any consistently stimulatory or inhibitory effects on FL and CB progenitors. In conclusion, important functional and biologic differences exist between FL, CB, and ABM progenitor cells, and these differences could have major implications for the use of these cell populations in preparative protocols of ex vivo expansion, transplantation strategies, or gene transfer experiments.

[Quality assessment indicators of cardiac surgeons' work; the validity of mortality rates]. / Rapportcijfers voor de hartchirurg; validiteit van waargenomen verschillen in sterfte.

OBJECTIVE: To determine the possibility of comparing the mortality rates of patients operated by different heart surgeons with each other. DESIGN: Retrospective cohort study. SETTING: Academic Medical Centre, Amsterdam, the Netherlands. PATIENTS AND METHODS: Clinical information, operation data and follow-up data on 783 patients who had undergone cardiac valve replacement, were collected from the clinical records. Aortic valve replacement had been performed in 446 patients (1979-1986) and mitral valve replacement in 337 patients (1980-1990). RESULTS: The one-year mortality rate was higher among patients operated on by heart surgeon A than among patients operated on by the other heart surgeons from the same team, viz. 16.4% and 9.5%, respectively, an absolute difference of 6.9%. The 95% confidence interval of the difference was 1.7-12.9. However, it was also found that the risk profiles of these patients of surgeon A differed from those of the other patients. After multivariate correction for this difference in risk profile, the difference in mortality was no longer statistically significant. CONCLUSION: The differences in mortality observed in our study could not be attributed to difference in quality of the heart surgeons, but were related with the risk profiles of the patients operated by one of them. Thorough analysis with correction for risks is necessary for the assessment of the quality of care, if the conclusions are not to be misleading.

Cardiac graft vasculopathy: aetiologic factors and therapeutic approaches.

Heart transplantation has become an accepted and successful treatment for end-stage heart disease with survival rates of 80-90% after one year and 70% after 5 years. During the early posttransplant period (6-12 months), patients are subject to two major complications: rejection and infection. Fortunately, a certain degree of graft tolerance develops, allowing the immunosuppressive therapy to be progressively tapered off with a concomitant decrease in infectious problems. Long-term survival, however, is largely dependent on the development of an accelerated atherosclerosis in the graft, which is believed to represent some kind of chronic rejection. This transplant vasculopathy is documented by means of coronary angiography with an incidence of approximately 5 to 10% per year. It is not surprising therefore that major interest has risen concerning risk factors promoting this pathology.